Effect of tetramethylpyrazine on hippocampal inflammatory responses in rats with sepsis-associated encephalopathy / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of tetramethylpyrazine on hippocampal inflammatory responses in rats with sepsis-associated encephalopathy.Methods:Sixty healthy male Sprague-Dawley rats, aged 12-14 weeks, weighing 240-270 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis-associated encephalopathy group (group SAE), low-dose tetramethylpyrazine group (group L-TMP), and high-dose tetramethylpyrazine group (group H-TMP). Sepsis-associated encephalopathy was induced by cecal ligation and puncture (CLP) in anesthetized rats.Tetramethylpyrazine 5 and 20 mg/kg were intraperitoneally injected once a day in L-TMP and H-TMP groups, respectively, at 5 days prior to CLP.Morris water maze test was performed at 1-5 days after CLP to assess the cognitive function, and the escape latency and ratio of time spent in the target quadrant were recorded.Five rats were sacrificed at 1 day after CLP, the brains were removed, and the hippocampi were isolated for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 by enzyme-linked immunosorbent assay.Rats were sacrificed after the end of Morris water maze test, and hippocampi were removed for detection of the expression of Toll-like receptor 1 (TLR1), activated caspase-3, Bax and Bcl-2 by using Western blot. Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the expression of TLR1, activated caspase-3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in group SAE, group L-TMP and group H-TMP, and the contents of IL-1β, TNF-α and IL-6 were significantly increased in group SAE and group L-TMP ( P<0.05). Compared with group SAE, the escape latency was significantly shortened, the ratio of time spent in the target quadrant was increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the expression of TLR1, activated caspase-3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in group L-TMP and group H-TMP ( P<0.05). Conclusion:The mechanism by which tetramethylpyrazine reduces sepsis-associated encephalopathy may be related to inhibiting hippocampal inflammatory responses in rats.